Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus

Arabadzisz, Dimitrula; Antal, Károly; Parpan, Franziska; Emri, Zsuzsa; Fritschy, Jean‐Marc

doi:10.1016/j.expneurol.2005.01.029

Cited by 134 publications

(160 citation statements)

References 52 publications

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“…Again, changes followed the major period of cell death, occurring during the pre--epileptic period and in the chronic epileptic mice. Contralateral hippocampal pathology has been reported in other mouse models of KA--induced status epilepticus ( Arabadzisz et al, 2005 and but is more surprising in the present model because of the lack of neuronal death or astrogliosis (present study and ). Inflammatory changes such as microgliosis and astrogliosis do occur in the contralateral hippocampus in the initial phase of epileptogenesis ) and in another model, neurochemical changes such as increased neuropeptide--Y were evident later in the latent and chronic phases in the contralateral hippocampus ( Arabadzisz et al, 2005).…”

Section: Introductionsupporting

confidence: 44%

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Heverin

Engel

Meaney³

et al. 2012

Brain Research

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Brain cholesterol homeostasis has been shown to be disrupted in neurodegenerative conditions such as Alzheimer's and Huntington's diseases. Investigations in animal models of seizure--induced brain injury suggest that brain cholesterol levels are altered by prolonged seizures (status epilepticus) and are a feature of the pathophysiology of temporal lobe epilepsy. The present study measured hippocampal sterol levels in a model of unilateral hippocampal injury triggered by focal--onset status epilepticus, and in chronically epileptic mice. Status epilepticus was induced by intra--amygdala microinjection of kainic acid and ipsilateral and contralateral hippocampus analyzed. No significant changes were found for ipsilateral or contralateral hippocampal levels of desmosterol or lathosterol at any time after SE as measured by gas chromatographymass spectrometry. 24S--hydroxycholesterol and cholesterol levels were unchanged up to 24 h after status epilepticus but were decreased in the ipsilateral hippocampus during early epileptogenesis and in chronically epileptic mice. Levels of cholesterol were also reduced in the contralateral hippocampus during epileptogenesis and in chronic epileptic mice. Treatment of mice with the anti--inflammatory cholesterol synthesis inhibitor lovastatin did not alter seizures during status epilepticus or seizure--induced neuronal death. Thus, changes to hippocampal cholesterol homeostasis predominantly begin during epileptogenesis, occur bi--laterally even when the initial precipitating injury is unilateral, and continue into the chronic epileptic period.

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Section: Introductionsupporting

confidence: 44%

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Heverin

Engel

Meaney³

et al. 2012

Brain Research

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“…An alternative explanation was that mutated channels are differentially expressed at GABAergic neurons, then provoking inhibition of these neurons that could lead to network disinhibition and seizures. In MTLE, seizures originate in the hippocampus para-hippocampal areas (partial seizures) with secondary generalization in some cases (Arabadzisz et al, 2005;Bernasconi et al, 2005;Cavazos and Cross, 2006;Kutlu et al, 2005). Therefore, the role of BK channel dysfunction will probably be different in generalized epilepsy with thalamo-cortical involvement.…”

Section: Discussionmentioning

confidence: 99%

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

Otalora¹,

Hernandez²,

Arshadmansab³

et al. 2008

Brain Research

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In the hippocampus, BK channels are preferentially localized in presynaptic glutamatergic terminals including mossy fibers where they are thought to play an important role regulating excessive glutamate release during hyperactive states. Large conductance calcium-activated potassium channels (BK, MaxiK, Slo) have recently been implicated in the pathogenesis of genetic epilepsy. However, the role of BK channels in acquired mesial temporal lobe epilepsy (MTLE) remains unknown. Here we used immunohistochemistry, laser scanning confocal microscopy (LSCM), western immunoblotting and RT-PCR to investigate the expression pattern of the alpha-pore forming subunit of BK channels in the hippocampus and cortex of chronically epileptic rats obtained by the pilocarpine model of MTLE. All epileptic rats experiencing recurrent spontaneous seizures exhibited a significant down-regulation of BK channel immunostaining in the mossy fibers at the hilus and stratum lucidum of the CA3 area. Quantitative analysis of immunofluorescence signals by LSCM revealed a significant 47% reduction in BK channel in epileptic rats when compared to age-matched non-epileptic control rats. These data correlate with a similar reduction in BK channel protein levels and transcripts in the cortex and hippocampus. Our data indicate a seizure-related down-regulation of BK channels in chronically epileptic rats. Further functional assays are necessary to determine whether altered BK channel expression is an acquired channelopathy or a compensatory mechanism affecting the network excitability in MTLE. Moreover, seizure-mediated BK down-regulation may disturb neuronal excitability and presynaptic control at glutamatergic terminals triggering exaggerated glutamate release and seizures.

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“…aFor details see text and Table 2.b30–100/h reported in a subsequent study by the same group 56c

Spike trains with a frequency of 1–3 Hz and/or duration <20 s were not considered in the quantitative analysis of epileptic activity.

This high frequency relates to only the low‐amplitude, high‐frequency part of the HPDs, but not to the slower high‐amplitude spike‐and‐wave pattern with which most HPDs start.

5–20 s = short HPD; >20 s = long HPD.

…”

Section: Tablementioning

confidence: 99%

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

Twele¹,

Töllner²,

Bankstahl³

et al. 2016

Epilepsia Open

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SummaryObjectiveMesial temporal lobe epilepsy (TLE) with hippocampal sclerosis is a predominant form of acquired epilepsy, characterized by recurrent simple and complex partial seizures that are often resistant to treatment. Mice developing spontaneous recurrent nonconvulsive and convulsive seizures after intrahippocampal injection of the excitotoxic glutamate agonist kainate are thought to represent a valuable model of mesial TLE. Epileptic electroencephalogram (EEG) activity recorded in this model from the kainate focus in the ipsilateral hippocampus is resistant to antiseizure drugs such as carbamazepine (CBZ). We compared the efficacy of CBZ in this model in two different mouse strains (FVB/N and NMRI). Furthermore, we evaluated whether changes in the definition of electrographic seizures affect the antiseizure efficacy of CBZ.MethodsAs in previous studies, two types of epileptic EEG activity were defined: high‐voltage sharp waves (HVSWs) and hippocampal paroxysmal discharges (HPDs). The characteristics of these paroxysmal EEG events in epileptic mice were compared with EEG criteria for nonconvulsive seizures in patients. For HVSWs, different spike frequencies, interevent intervals, and amplitudes were used as inclusion and exclusion criteria. In addition to CBZ, some experiments were performed with diazepam (DZP) and phenobarbital (PB).ResultsFemale epileptic FVB/N mice predominantly exhibited frequent HVSWs, but only infrequent HPDs or secondarily generalized convulsive seizures. Slight changes in HVSW definition determined whether they were resistant or responsive to CBZ. Male NMRI mice exhibited both HVSWs and HPDs. HVSWs were more resistant than HPDs to suppression by CBZ. Both types of epileptic EEG activity were rapidly suppressed by DZP and PB.SignificanceThe data demonstrate that focal electrographic seizures in the intrahippocampal kainate mouse model are less resistant than previously thought. Both mouse strain and the criteria chosen for definition of EEG seizures determine whether such seizures are drug‐resistant or ‐responsive.

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Epileptogenesis and chronic seizures in a mouse model of temporal lobe epilepsy are associated with distinct EEG patterns and selective neurochemical alterations in the contralateral hippocampus

Cited by 134 publications

References 52 publications

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Bi-lateral changes to hippocampal cholesterol levels during epileptogenesis and in chronic epilepsy following focal-onset status epilepticus in mice

Down-regulation of BK channel expression in the pilocarpine model of temporal lobe epilepsy

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

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